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Kang YW, Baek YH, Lee JH, Roh YH, Kwon HJ, Moon SY, Son MK, Jeong JS. Assessing the Utility of Acoustic Radiation Force Impulse in the Evaluation of Non-Alcoholic Fatty Liver Disease with Severe Obesity or Steatosis. Diagnostics (Basel) 2024; 14:1083. [PMID: 38893610 PMCID: PMC11171891 DOI: 10.3390/diagnostics14111083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/16/2024] [Accepted: 05/20/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients. AIM This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis. METHODS This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score. RESULTS ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH. CONCLUSIONS In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD.
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Affiliation(s)
- Yeo Wool Kang
- Department of Internal Medicine, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea; (Y.W.K.); (J.H.L.); (S.Y.M.)
| | - Yang Hyun Baek
- Department of Internal Medicine, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea; (Y.W.K.); (J.H.L.); (S.Y.M.)
| | - Jong Hoon Lee
- Department of Internal Medicine, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea; (Y.W.K.); (J.H.L.); (S.Y.M.)
| | - Young Hoon Roh
- Department of General Surgery, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea;
| | - Hee Jin Kwon
- Department of Radiology, Dong-A University College of Medicine, 1,3-ga Dongdaesindong, Seo-gu, Busan 49201, Republic of Korea;
| | - Sang Yi Moon
- Department of Internal Medicine, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea; (Y.W.K.); (J.H.L.); (S.Y.M.)
| | - Min Kook Son
- Department of Physiology, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea;
| | - Jin Sook Jeong
- Department of Pathology, Dong-A University College of Medicine, 32 Daeshingongwonro, Seo-gu, Busan 49201, Republic of Korea;
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Loomba R, Clark G, Teckman J, Ajmera V, Behling C, Brantly M, Brenner D, D'Armiento J, Fried MW, Iyer JS, Mandorfer M, Rockey DC, Tincopa M, Vuppalanchi R, Younossi Z, Krag A, Turner AM, Strnad P. Review article: New developments in biomarkers and clinical drug development in alpha-1 antitrypsin deficiency-related liver disease. Aliment Pharmacol Ther 2024; 59:1183-1195. [PMID: 38516814 DOI: 10.1111/apt.17967] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/04/2024] [Accepted: 03/12/2024] [Indexed: 03/23/2024]
Abstract
BACKGROUND Alpha-1 antitrypsin liver disease (AATLD) occurs in a subset of patients with alpha-1 antitrypsin deficiency. Risk factors for disease progression and specific pathophysiologic features are not well known and validated non-invasive assessments for disease severity are lacking. Currently, there are no approved treatments for AATLD. AIMS To outline existing understanding of AATLD and to identify knowledge gaps critical to improving clinical trial design and development of new treatments. METHODS This report was developed following a multi-stakeholder forum organised by the Alpha-1 Antitrypsin Deficiency Related Liver Disease Expert Panel in which experts presented an overview of the available literature on this topic. RESULTS AATLD results from a 'gain of toxic function' and primarily manifests in those with the homozygous Pi*ZZ genotype. Accumulation of misfolded 'Z' AAT protein in liver cells triggers intracellular hepatocyte injury which may ultimately lead to hepatic fibrosis. Male gender, age over 50 years, persistently elevated liver tests, concomitant hepatitis B or C virus infection, and metabolic syndrome, including obesity and type 2 diabetes mellitus, are known risk factors for adult AATLD. While the gold standard for assessing AATLD disease activity is liver histology, less invasive measures with low intra- and inter-observer variability are needed. Measurement of liver stiffness shows promise; validated thresholds for staging AATLD are in development. Such advances will help patients by enabling risk stratification and personalised surveillance, along with streamlining the development process for novel therapies. CONCLUSIONS This inaugural forum generated a list of recommendations to address unmet needs in the field of AATLD.
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Affiliation(s)
- Rohit Loomba
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, San Diego, California, USA
| | - Ginger Clark
- Department of Medicine, University of Florida, Gainesville, Florida, USA
| | - Jeff Teckman
- Pediatrics and Biochemistry, St. Louis University School of Medicine, Saint Louis, Missouri, USA
| | - Veeral Ajmera
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, San Diego, California, USA
| | - Cynthia Behling
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, San Diego, California, USA
- Pacific Rim Pathology Lab, San Diego, California, USA
| | - Mark Brantly
- Division of Pulmonary, Critical Care & Sleep Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
| | - David Brenner
- Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA
| | - Jeanine D'Armiento
- Department of Medicine, Columbia University Medical Center, New York, New York, USA
| | | | | | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Don C Rockey
- Medical University of South Carolina, Charleston, South Carolina, USA
| | - Monica Tincopa
- University of California San Diego, San Diego, California, USA
| | - Raj Vuppalanchi
- Indiana University School of Medicine, Indianapolis, Indiana, USA
| | | | | | | | - Pavel Strnad
- University Hospital RWTH Aachen, Healthcare Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
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3
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Qamar M, Fatima A, Tauseef A, Yousufzai MI, Liaqat I, Naqvi Q. Comparative and Predictive Significance of Serum Leptin Levels in Non-alcoholic Fatty Liver Disease. Cureus 2024; 16:e57943. [PMID: 38738048 PMCID: PMC11084851 DOI: 10.7759/cureus.57943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2024] [Indexed: 05/14/2024] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) has emerged as the single most common chronic non-viral liver disease. The burden of the disease on healthcare-providing services has increased tremendously. Although a liver biopsy is the most authentic laboratory investigation for scoring the disease progression, it is an invasive technique. Researchers are vigorously working to find alternate markers for the scoring purpose. Despite the importance and association of leptin with metabolic syndrome and its related disorders, there have been relatively fewer studies on serum leptin and its association with NAFLD. Objective This study aimed to investigate variations in serum leptin levels between subjects with and without fibrosis in NAFLD and to assess the predictive value of serum leptin levels in NAFLD subjects. Materials and methods The study comprised 130 NAFLD subjects from two tertiary care hospitals in Lahore along with 86 healthy controls that were age, gender, and BMI matched with the subjects. Based on the NAFLD fibrosis score (NFS), the subjects were divided into two sub-groups, subjects with simple steatosis and those with fibrosis. Fasting serum leptin, glucose, and insulin levels were measured using enzyme-linked immunosorbent assay (ELISA). The Kruskal-Wallis test was applied to find differences between the three groups and Fisher's exact test for categorical comparison. To assess the predictive value of serum leptin for steatosis and fibrosis in NAFLD subjects, receiver operation characteristic (ROC) curve analysis was implemented. Results The difference in serum leptin level was statistically highly significant (p-value <0.001), with leptin levels of 10 (17.1) ng/mL among controls, 20.5 (21) ng/mL in simple steatosis, and 21 (28.6) ng/mL in fibrosis. The area under the ROC curve was 0.67 and 0.52 for steatosis and fibrosis, respectively. The cut-off value of 12.2 ng/mL showed 70% sensitivity and 50% specificity for steatosis, while at a threshold of 18 ng/mL, leptin demonstrated 40% sensitivity and specificity for fibrosis. Conclusion In conclusion, this study found that serum leptin levels are higher in NAFLD subjects compared to healthy controls, and it is a good independent predictor for the detection of liver steatosis.
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Affiliation(s)
- Mehwish Qamar
- Physiology, Islam Medical and Dental College, Sialkot, PAK
| | - Abeer Fatima
- Physiology, Services Institute of Medical Sciences, Lahore, PAK
| | - Ambreen Tauseef
- Physiology, Combined Military Hospital Lahore Medical College and Institute of Dentistry, Lahore, PAK
| | | | - Ibrahim Liaqat
- Physiology, Islam Medical and Dental College, Sialkot, PAK
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Lekakis V, Papatheodoridis GV. Natural history of metabolic dysfunction-associated steatotic liver disease. Eur J Intern Med 2024; 122:3-10. [PMID: 37940495 DOI: 10.1016/j.ejim.2023.11.005] [Citation(s) in RCA: 53] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 10/31/2023] [Accepted: 11/03/2023] [Indexed: 11/10/2023]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), which has been the term for non-alcoholic fatty liver disease (NAFLD) since June 2023, represents the most common liver disease worldwide and is a leading cause of liver-related morbidity and mortality. A thorough knowledge of the disease's natural history is required to promptly stratify patients' risks, since MASLD is a multifaceted disorder with a broad range of clinical phenotypes. The histological disease spectrum ranges from isolated hepatic steatosis, currently named as metabolic dysfunction-associated steatotic liver (MASL), to metabolic dysfunction-associated steatohepatitis (MASH) and eventually may accumulate hepatic fibrosis and develop cirrhosis and/or hepatocellular carcinoma (HCC). Several risk factors for fibrosis progression have been identified, while the disease's progression displays notable dynamism and bidirectionality. When compared to the general population, all MASLD histological stages are substantially related with greater overall mortality, and this association exhibits a disease severity-dependent pattern. Interestingly, the fibrosis stage is the most accurate predictor of mortality among MASLD patients. The mortality attributed to MASLD predominantly stems from issues linked with the liver and cardiovascular system, as well as HCC and extrahepatic cancers. In light of the disease natural course, it is crucial to prioritize the identification of at-risk patients for disease progression in order to effectively address and change modifiable risk factors, hence mitigating disease complications. Further investigation is required to define the phenotype of rapid progressors more precisely as well as to improve risk stratification for HCC in non-cirrhotic individuals.
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Affiliation(s)
- Vasileios Lekakis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 17 Agiou Thoma Street, Athens 11527, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", 17 Agiou Thoma Street, Athens 11527, Greece.
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Brozat JF, Ntanios F, Malhotra D, Dagenais S, Katchiuri N, Emir B, Tacke F. NAFLD and NASH are obesity-independent risk factors in COVID-19: Matched real-world results from the large PINC AI™ Healthcare Database. Liver Int 2024; 44:715-722. [PMID: 38110709 DOI: 10.1111/liv.15815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 11/09/2023] [Accepted: 11/25/2023] [Indexed: 12/20/2023]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are potential risk factors for severe pneumonia and other infections. Available data on the role of NAFLD/NASH in worsening outcomes for COVID-19 are controversial and might be confounded by comorbidities. METHODS We used the PINC AI™ Healthcare Data Special Release (PHD-SR) to identify patients with COVID-19 (ICD-10) at approximately 900 hospitals in the United States. We performed exact matching (age, gender, and ethnicity) for patients with or without NAFLD/NASH, adjusting for demographics (admission type, region) and comorbidities (e.g., obesity, diabetes) through inverse probability of treatment weighting and then analysed hospitalisation-related outcomes. RESULTS Among 513 623 patients with SARS-CoV-2 (COVID-19), we identified 14 667 with NAFLD/NASH who could be matched to 14 667 controls. Mean age was 57.6 (±14.9) years, 50.8% were females and 43.7% were non-Hispanic whites. After matching, baseline characteristics (e.g., age, ethnicity, and gender) and comorbidities (e.g., hypertension, obesity, diabetes, and cardiovascular disease) were well balanced (standard difference (SD) <.10), except for cirrhosis and malignancies. Patients with COVID-19 and NAFLD/NASH had higher FIB-4 scores, a significantly longer hospital length of stay (LOS) and intensive care LOS than controls (9.4 vs. 8.3 days, and 10.4 vs. 9.3, respectively), even after adjusting for cirrhosis and malignancies. Patients with COVID-19 and NAFLD/NASH also had significantly higher risk of needing invasive mandatory ventilation (IMV) (odds ratio 1.0727; 95% CI 1.0095-1.1400). Other outcomes were similar in both groups. CONCLUSIONS In this large real-world cohort of patients hospitalised for COVID-19 in the United States, NAFLD/NASH were obesity-independent risk factors for complicated disease courses.
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Affiliation(s)
- Jonathan F Brozat
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
| | | | | | | | | | | | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany
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Balogun O, Wang JY, Shaikh ES, Liu K, Stoyanova S, Memel ZN, Schultz H, Mun L, Bertman J, Rogen CA, Ibrahim MK, Berschback M, Uche-Anya E, Wilechansky R, Simon TG, Corey KE. Effect of combined tobacco use and type 2 diabetes mellitus on prevalent fibrosis in patients with MASLD. Hepatol Commun 2023; 7:e0300. [PMID: 37889558 PMCID: PMC10615418 DOI: 10.1097/hc9.0000000000000300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 09/07/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND Several studies have investigated the independent effect of cigarette smoking or type 2 diabetes mellitus (T2DM) on MASLD. However, the interaction effect between tobacco consumption and T2DM on MASLD severity remains underexplored. In this study, we assessed the combined effect of tobacco use and T2DM on hepatic fibrosis in MASLD. METHODS We conducted a single-center retrospective cross-sectional analysis of eligible participants from the Mass General Brigham Fibroscan© database. The participants were divided into 3 groups: those with T2DM and a history of tobacco use (primary exposure group), those with T2DM but no history of tobacco use (secondary exposure group), and those without T2DM and no history of tobacco use (reference group). An additional model was developed, which included a fourth group, participants with a history of tobacco use but no T2DM. The likelihood of fibrosis was determined using a defined fibrosis-4 index cutoff value of 1.3. In addition, we computed the estimated marginal means for liver stiffness measurement and compared the values among the exposure groups. Bivariable and multivariable logistic regression models were used to explore the associations between the exposure groups and the risk for hepatic fibrosis. RESULTS Overall, 598 individuals were enrolled in the study. The bivariable logistic regression model revealed a significant independent association between T2DM, combined smoking and T2DM, and the outcome of interest, fibrosis. Age, sex, metabolic syndrome, aspirin use, statin use, hemoglobin A1C (A1C), and total bilirubin level were also significantly associated with fibrosis. In the adjusted fibrosis-4 multivariable model (comparing exposure groups to controls), cigarette smoking and T2DM interaction had higher odds of prevalent fibrosis (aOR, 3.04; 95% CI, 1.62-5.76), compared to those with T2DM alone (aOR 2.28; 95% CI, 1.37-3.85). The continuous liver stiffness measurement comparison across the exposure group showed an estimated marginal means of 6.26 (95% CL: 5.58-6.94), 7.54 (95% CL: 6.78-8.30), and 7.88 (6.78-8.99) for the reference group, T2DM only group, and tobacco-T2DM group, respectively. The diabetes-only group and the combined tobacco-T2DM group had statistically significant associations with liver stiffness measurement (p values: 0.013 and 0.014, respectively). CONCLUSION Although diabetes is independently associated with hepatic fibrosis in patients with MASLD, the combination of tobacco consumption and diabetes is associated with a higher prevalence of fibrosis. Therefore, lifestyle change through tobacco use cessation in patients with diabetes could be beneficial in reducing the incidence of liver fibrosis among individuals with MASLD.
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Affiliation(s)
- Oluwafemi Balogun
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Jeffrey Y. Wang
- George Washington University School of Medicine, Washington D.C., 2001
| | - Emad S. Shaikh
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
- Harvard Medical School, Boston Massachusetts, USA
- Department of Medicine, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Karine Liu
- Harvard Medical School, Boston Massachusetts, USA
- Department of Medicine, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Stefania Stoyanova
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Zoe N. Memel
- University of California San Francisco Medical Center, San Francisco, California, USA
| | - Hayley Schultz
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Lisa Mun
- Central Michigan University College of Medicine, Mt Pleasant, Michigan
| | - Jack Bertman
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Cheryl A. Rogen
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Maryam K. Ibrahim
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
- Harvard Medical School, Boston Massachusetts, USA
- Department of Medicine, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Madeline Berschback
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
- Harvard Medical School, Boston Massachusetts, USA
- Department of Medicine, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Eugenia Uche-Anya
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
- Harvard Medical School, Boston Massachusetts, USA
- Department of Medicine, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Robert Wilechansky
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
- Harvard Medical School, Boston Massachusetts, USA
- Department of Medicine, Massachusetts General Hospital, Boston Massachusetts, USA
| | - Tracey G. Simon
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
- Harvard Medical School, Boston Massachusetts, USA
- Department of Medicine, Massachusetts General Hospital, Boston Massachusetts, USA
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston Massachusetts, USA
| | - Kathleen E. Corey
- Department of Medicine, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Boston Massachusetts, USA
- Harvard Medical School, Boston Massachusetts, USA
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston Massachusetts, USA
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Głuszyńska P, Łukaszewicz A, Diemieszczyk I, Chilmończyk J, Reszeć J, Citko A, Szczerbiński Ł, Krętowski A, Razak Hady H. The Effect of Laparoscopic Sleeve Gastrectomy on the Course of Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients during One Year of Follow Up. J Clin Med 2023; 12:4122. [PMID: 37373815 DOI: 10.3390/jcm12124122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/15/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Morbid obesity co-exists with non-alcoholic fatty liver disease in up to 90% of cases. Laparoscopic sleeve gastrectomy leads to a reduction in body mass and thus may improve the course of non-alcoholic fatty liver disease. The aim of this study was to evaluate the effect of laparoscopic sleeve gastrectomy on the resolution of non-alcoholic fatty liver disease. METHODS The study included 55 patients with non-alcoholic fatty liver disease who underwent laparoscopic sleeve gastrectomy at a tertiary institution. The analysis consisted of preoperative liver biopsy, abdominal ultrasound, weight loss parameters, Non-Alcoholic Fatty Liver Fibrosis Score and selected laboratory parameters. RESULTS Before the surgery, 6 patients were diagnosed with grade 1 liver steatosis, 33 patients with grade 2 and 16 patients with grade 3. One year after the surgery, only 21 patients had features of liver steatosis at ultrasound. All weight loss parameters showed statistically significant changes during the observation; the median percentage of total weight loss was 31.0% (IQR: 27.5; 34.5) with p = 0.0003, the median percentage of excess weight loss was 61.8% (IQR: 52.4; 72.3) with p = 0.0013 and the median percentage of excess body mass index loss was 71.0% (IQR: 61.3; 86.9) with p = 0.0036 12 months after laparoscopic sleeve gastrectomy. The median Non-Alcoholic Fatty Liver Fibrosis Score at baseline was 0.2 (IQR: -0.8; 1.0) and decreased to -1.6 (IQR: -2.4; -0.4) (p < 0.0001). Moderate negative correlations between Non-Alcoholic Fatty Liver Fibrosis Score and percentage of total weight loss (r = -0.434, p < 0.0001), percentage of excess weight loss (r = -0.456, p < 0.0001) and percentage of excess body mass index loss (r = -0.512, p < 0.0001) were found. CONCLUSIONS The study supports the thesis that laparoscopic sleeve gastrectomy is an effective method for treatment of non-alcoholic fatty liver disease in patients with morbid obesity.
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Affiliation(s)
- Paulina Głuszyńska
- Department of General and Endocrine Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Aleksander Łukaszewicz
- Department of General and Endocrine Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Inna Diemieszczyk
- Department of Surgery, Independent Public Health Care Center in Lapy, 18-100 Lapy, Poland
| | - Jan Chilmończyk
- Department of General and Endocrine Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Joanna Reszeć
- Department of Medical Pathomorphology, Medical University of Bialystok, 15-269 Bialystok, Poland
| | - Anna Citko
- Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Łukasz Szczerbiński
- Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland
- Department of Endocrinology, Diabetology and Internal Diseases, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Adam Krętowski
- Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland
- Department of Endocrinology, Diabetology and Internal Diseases, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Hady Razak Hady
- Department of General and Endocrine Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland
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Li L, Song Y, Shi Y, Sun L. Thyroid Hormone Receptor-β Agonists in NAFLD Therapy: Possibilities and Challenges. J Clin Endocrinol Metab 2023; 108:1602-1613. [PMID: 36746649 DOI: 10.1210/clinem/dgad072] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 02/01/2023] [Accepted: 02/02/2023] [Indexed: 02/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a progressive metabolic liver disease with an unknown pathogenesis and no FDA-approved drug treatment to date. Hypothyroidism has been identified as a risk factor for NAFLD as thyroxine is required for regulating metabolism in adults. Thyroxine has been shown to reduce fat in the livers of murine models with experimentally induced NAFLD. The use of synthetic thyroxine has been shown to increase lipid metabolism leading to weight loss; however, thyroxine has also been shown to cause many side effects, especially in the heart. Overcoming these cardiac side effects involves designing agonists specific to one of the 2 gene subtypes for the thyroid hormone (TH) receptor (TR), TRβ. While the other TH receptor subtype, TRα, is mainly expressed in the heart and is responsible for thyroxine's cardiac function, TRβ is mainly expressed in the liver and is involved in liver function. Using TRβ-specific agonists to treat NAFLD can prevent cardiac and other adverse side effects. Several TRβ-specific agonists have shown positive therapeutic effects in NAFLD animal models and have entered clinical trials. We seek to provide a comprehensive updated reference of TRβ-specific agonists in this review and explore the future therapeutic potential of TRβ-specific activation in the treatment of NAFLD.
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Affiliation(s)
- Limei Li
- Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
| | - Yan Song
- Department of Endocrinology and Metabolism, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Yongquan Shi
- Department of Endocrinology and Metabolism, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Liangliang Sun
- Department of Endocrinology and Metabolism, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
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Timaná J, Chahuara H, Basavarajappa L, Basarab A, Hoyt K, Lavarello R. Simultaneous imaging of ultrasonic relative backscatter and attenuation coefficients for quantitative liver steatosis assessment. Sci Rep 2023; 13:8898. [PMID: 37264043 DOI: 10.1038/s41598-023-33964-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 04/21/2023] [Indexed: 06/03/2023] Open
Abstract
Prevalence of liver disease is continuously increasing and nonalcoholic fatty liver disease (NAFLD) is the most common etiology. We present an approach to detect the progression of liver steatosis based on quantitative ultrasound (QUS) imaging. This study was performed on a group of 55 rats that were subjected to a control or methionine and choline deficient (MCD) diet known to induce NAFLD. Ultrasound (US) measurements were performed at 2 and 6 weeks. Thereafter, animals were humanely euthanized and livers excised for histological analysis. Relative backscatter and attenuation coefficients were simultaneously estimated from the US data and envelope signal-to-noise ratio was calculated to train a regression model for: (1) fat fraction percentage estimation and (2) performing classification according to Brunt's criteria in grades (0 <5%; 1, 5-33%; 2, >33-66%; 3, >66%) of liver steatosis. The trained regression model achieved an [Formula: see text] of 0.97 (p-value < 0.01) and a RMSE of 3.64. Moreover, the classification task reached an accuracy of 94.55%. Our results suggest that in vivo QUS is a promising noninvasive imaging modality for the early assessment of NAFLD.
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Affiliation(s)
- José Timaná
- Laboratorio de Imágenes Médicas, Pontificia Universidad Católica del Perú, Lima, Peru
| | - Hector Chahuara
- Laboratorio de Imágenes Médicas, Pontificia Universidad Católica del Perú, Lima, Peru
| | - Lokesh Basavarajappa
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Adrian Basarab
- INSA-Lyon, UCBL, CNRS, Inserm, CREATIS UMR 5220 U1294, Université de Lyon, Villeurbanne, France
| | - Kenneth Hoyt
- Department of Bioengineering, University of Texas at Dallas, Richardson, TX, USA
| | - Roberto Lavarello
- Laboratorio de Imágenes Médicas, Pontificia Universidad Católica del Perú, Lima, Peru.
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10
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Hatto M, Ivano VK, Gestic MA, Utrini MP, Chaim FDM, Callejas-Neto F, Chaim EA, Cazzo E. Application of Scores Assessing Histological Activity and Estimated Long-Term Risk Analysis of Hepatic Decompensation of Non-Alcoholic Fatty Liver Disease in Individuals Undergoing Bariatric Surgery. Obes Surg 2023; 33:1580-1586. [PMID: 37004688 DOI: 10.1007/s11695-023-06568-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 03/23/2023] [Accepted: 03/28/2023] [Indexed: 04/04/2023]
Abstract
BACKGROUND Histological scores can estimate disease staging, allowing a standardization of the assessment of non-alcoholic fatty liver disease (NAFLD). The prediction of risk of NAFLD progression is relevant to allow the planning of interventions. OBJECTIVE To analyze the application of the Iowa NAFLD decompensation risk score, the NAFLD activity score (NAS), and steatosis-activity-fibrosis score (SAF) and to assess correlations between these scores. METHODS This is a retrospective cross-sectional study enrolling 76 individuals who underwent bariatric surgery at a tertiary university hospital. Liver biopsy was performed during procedures; histological scores were then assessed. The Iowa score was calculated using age, diabetes, and platelet count. RESULTS 89.5% were female and mean age was 39.1 ± 9.6 years. Mean BMI was 38.2 ± 3.7 kg/m2. Steatosis (92.1%), hepatocellular ballooning (93.4%), lobular inflammation (93.4%), and fibrosis (97.4%) were the commonest histopathological findings. According to NAS, 22.4% had definite non-alcoholic steatohepatitis (NASH). According to SAF, 89.5% had moderate or severe NAFLD. The mean risks of NAFLD decompensation at 5, 10, and 12 years were 0.8%, 2.5%, and 2.9%, respectively. The group whose risk of decompensation was above 10% comprised 2.6% and 5.3% at 10 and 12 years, respectively. The severity assessed by SAF significantly associated with definite NASH diagnosis through NAS (p < 0.001). Iowa score did not correlate with both NAS/SAF scores. CONCLUSION The Iowa score demonstrated that individuals with obesity present with a significant long-term risk of NAFLD-related events. There were high rates of moderate/severe forms of NAFLD assessed by NAS and SAF scores. There were no significant correlations between Iowa and NAS/SAF scores.
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Affiliation(s)
- Marcelo Hatto
- Depatment of Surgery, School of Medical Sciences, State University of Campinas (UNICAMP), Sao Paulo, Campinas, Brazil
| | - Victor Kenzo Ivano
- Depatment of Surgery, School of Medical Sciences, State University of Campinas (UNICAMP), Sao Paulo, Campinas, Brazil
| | - Martinho Antonio Gestic
- Depatment of Surgery, School of Medical Sciences, State University of Campinas (UNICAMP), Sao Paulo, Campinas, Brazil
| | - Murillo Pimentel Utrini
- Depatment of Surgery, School of Medical Sciences, State University of Campinas (UNICAMP), Sao Paulo, Campinas, Brazil
| | - Felipe David Mendonça Chaim
- Depatment of Surgery, School of Medical Sciences, State University of Campinas (UNICAMP), Sao Paulo, Campinas, Brazil
| | - Francisco Callejas-Neto
- Depatment of Surgery, School of Medical Sciences, State University of Campinas (UNICAMP), Sao Paulo, Campinas, Brazil
| | - Elinton Adami Chaim
- Depatment of Surgery, School of Medical Sciences, State University of Campinas (UNICAMP), Sao Paulo, Campinas, Brazil
| | - Everton Cazzo
- Depatment of Surgery, School of Medical Sciences, State University of Campinas (UNICAMP), Sao Paulo, Campinas, Brazil.
- Rua Alexander Fleming, S/No Cidade Universitária Zeferino Vaz, Sao Paulo, CEP, Campinas, 13085-000, Brazil.
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Gheorghe L, Nemteanu R, Clim A, Botnariu GE, Costache II, Plesa A. Risk Scores for Prediction of Major Cardiovascular Events in Non-Alcoholic Fatty Liver Disease: A No Man's Land? Life (Basel) 2023; 13:life13040857. [PMID: 37109386 PMCID: PMC10146692 DOI: 10.3390/life13040857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/18/2023] [Accepted: 03/21/2023] [Indexed: 04/29/2023] Open
Abstract
Over the past 100 years, cardiovascular disease (CVD) has become a leading cause of mortality and morbidity in developed countries, and similar trends have occurred for chronic liver disease. Subsequent research also indicated that people with non-alcoholic fatty liver disease (NAFLD) had a twofold increased risk of CV events and that this risk was doubled in those with liver fibrosis. However, no validated CVD risk score specific for NAFLD patients has yet been validated, as traditional risk scores tend to underestimate the CV risk in NAFLD patients. From a practical perspective, identifying NAFLD patients and assessing severity of liver fibrosis when concurrent atherosclerotic risk factors are already established may serve as an important criterion in new CV risk scores. The current review aims to assess current risk scores and their utility for the prediction of CV events among patients with NAFLD.
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Affiliation(s)
- Liliana Gheorghe
- Department of Radiology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Radiology Clinic, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Roxana Nemteanu
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania
| | - Andreea Clim
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Gina Eosefina Botnariu
- Diabetes, Nutrition and Metabolic Diseases Department, University of Medicine and Pharmacy "Gr. T. Popa", 700115 Iasi, Romania
| | - Irina Iuliana Costache
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Cardiology Clinic, "St. Spiridon" County Clinical Emergency Hospital, 700111 Iasi, Romania
| | - Alina Plesa
- Medical I Department, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
- Institute of Gastroenterology and Hepatology, Saint Spiridon Hospital, 700111 Iasi, Romania
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12
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Hiruma S, Shigiyama F, Kumashiro N. Empagliflozin versus sitagliptin for ameliorating intrahepatic lipid content and tissue-specific insulin sensitivity in patients with early-stage type 2 diabetes with non-alcoholic fatty liver disease: A prospective randomized study. Diabetes Obes Metab 2023; 25:1576-1588. [PMID: 36749298 DOI: 10.1111/dom.15006] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 01/24/2023] [Accepted: 02/02/2023] [Indexed: 02/08/2023]
Abstract
AIM To compare the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors on ectopic fat accumulation and tissue-specific insulin sensitivity. MATERIALS AND METHODS This randomized controlled trial enrolled 44 patients with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). They were randomly assigned to receive either empagliflozin 10 mg/day or sitagliptin 100 mg/day for 12 weeks. The primary endpoint was the change in intrahepatic lipid content (IHL) measured using proton magnetic resonance spectroscopy (1 H-MRS). The secondary endpoints included intramuscular and extramuscular lipid content seen in 1 H-MRS, body composition seen through dual-energy X-ray absorptiometry and tissue-specific insulin sensitivity shown through hyperinsulinaemic-euglycaemic clamp using stable isotopic glucose. Liver biopsy samples were pathologically evaluated at baseline. RESULTS At baseline, the mean duration of diabetes, HbA1c level and IHL were 3.7 years, 7.2% and 20.9%, respectively. The median NAFLD activity score was 3.0. IHL was significantly more decreased in the empagliflozin group than that in the sitagliptin group (between-group difference was -5.2% ± 1.1% and -1.9% ± 1.2%, respectively, (95% confidence interval); -3.3 (-6.5, -0.1), P = .044). However, there were no significant between-group differences in the change of insulin sensitivity in the liver, muscle or adipose tissues. Interestingly, hepatic insulin sensitivity was significantly increased only in the empagliflozin group and was significantly negatively associated with the change in IHL. CONCLUSIONS Empagliflozin significantly improves hepatic steatosis compared with sitagliptin, and this may protect against subsequent hepatic insulin resistance. Early administration of SGLT2 inhibitors is preferable for T2D patients with NAFLD.
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Affiliation(s)
- Shigenori Hiruma
- Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan
| | - Fumika Shigiyama
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan
| | - Naoki Kumashiro
- Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan
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13
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Chen J, Yu S, Lang Z, Jin Y, Zhou G, Tao Q, Wang X, Zheng J. Development and validation of a potential biomarker to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B. J Med Virol 2023; 95:e28239. [PMID: 36258661 DOI: 10.1002/jmv.28239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 09/16/2022] [Accepted: 10/16/2022] [Indexed: 01/12/2023]
Abstract
We aimed to develop and validate a novel combined score to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B (CHB). In this study, a total of 331 CHB patients from three cohorts who underwent liver biopsy were enrolled, and the Scheuer system was used for liver fibrosis classification. The combined score was derived by principal component analysis of key differentially expressed genes. For significant liver fibrosis (≥S2), the areas under the receiver operating characteristics curves (AUROCs) of the combined score were 0.838, 0.842, and 0.881 in the three cohorts, respectively. And for advanced liver fibrosis (≥S3), the AUROCs were 0.794, 0.801, and 0.901, respectively. Compared with the results of AUROCs for aspartate aminotransferase≥to≥platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) in the validation cohorts, better clinical diagnostic value for assessing the progression of liver fibrosis was found in the combined score. Additionally, univariate ordered logistic regression analysis indicated that the combined score could serve as a more superior and stable risk factor than APRI and FIB-4 in the assessment of liver fibrosis. For CHB patients with normal alanine aminotransferase (ALT), our results further emphasized the diagnostic value of the combined score for significant fibrosis (≥S2) and advanced fibrosis (≥S3). Moreover, it was found that patients with the high combined score, who were associated with the advanced fibrosis stage, had higher levels of drug sensitivity and immune checkpoint expression. In conclusion, the novel combined score could serve as a potential biomarker and contribute to improving the assessment of fibrosis stage in CHB patients.
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Affiliation(s)
- Ji Chen
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Suhui Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhichao Lang
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yan Jin
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Guangyao Zhou
- Department of Infectious Diseases, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Qiqi Tao
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiaodong Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jianjian Zheng
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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14
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Yan M, Man S, Ma L, Gao W. Comprehensive molecular mechanisms and clinical therapy in nonalcoholic steatohepatitis: An overview and current perspectives. Metabolism 2022; 134:155264. [PMID: 35810782 DOI: 10.1016/j.metabol.2022.155264] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 06/28/2022] [Accepted: 07/04/2022] [Indexed: 10/17/2022]
Abstract
Our understanding of nonalcoholic steatohepatitis (NASH) pathophysiology continues to advance rapidly. Given the complexity of the pathogenesis of NASH, the field has moved from describing the single pathogenesis of NASH to deeply phenotyping with a description of the multi-mechanism and multi-target pathogenesis that includes glucose, lipid and cholesterol metabolism, fibrotic progression, inflammation, immune reaction and apoptosis. To make the picture more complex, the pathogenesis of NASH involves pathological connections between the liver and several organs such as the adipose, pancreas, kidney and gut. Numerous pharmacologic candidates have been tested in clinical trials and have generated some positive results. Importantly, PPAR as triglyceride synthesis inhibitor and FXR as bile acids synthesis inhibitor have displayed beneficial effects on candidates for lipid and cholesterol metabolism. Although the efficacy of these drugs has been affirmed, serious side effects hinder their further development. It is a particularly important task to carry out the in-depth long-term research. Additionally, drug combination increases response rate and reduces side effects of a single drug. Mastering the advantages and limitations of clinical candidate drugs and continuous improvement and innovation are necessary to formulate a new strategy for the future treatment of NASH.
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Affiliation(s)
- Mengyao Yan
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China
| | - Shuli Man
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
| | - Long Ma
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
| | - Wenyuan Gao
- Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China.
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15
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NAFLD: Mechanisms, Treatments, and Biomarkers. Biomolecules 2022; 12:biom12060824. [PMID: 35740949 PMCID: PMC9221336 DOI: 10.3390/biom12060824] [Citation(s) in RCA: 205] [Impact Index Per Article: 68.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is one of the most common causes of liver diseases worldwide. NAFLD is growing in parallel with the obesity epidemic. No pharmacological treatment is available to treat NAFLD, specifically. The reason might be that NAFLD is a multi-factorial disease with an incomplete understanding of the mechanisms involved, an absence of accurate and inexpensive imaging tools, and lack of adequate non-invasive biomarkers. NAFLD consists of the accumulation of excess lipids in the liver, causing lipotoxicity that might progress to metabolic-associated steatohepatitis (NASH), liver fibrosis, and hepatocellular carcinoma. The mechanisms for the pathogenesis of NAFLD, current interventions in the management of the disease, and the role of sirtuins as potential targets for treatment are discussed here. In addition, the current diagnostic tools, and the role of non-coding RNAs as emerging diagnostic biomarkers are summarized. The availability of non-invasive biomarkers, and accurate and inexpensive non-invasive diagnosis tools are crucial in the detection of the early signs in the progression of NAFLD. This will expedite clinical trials and the validation of the emerging therapeutic treatments.
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16
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Blank V, Petroff D, Boehlig A, Heinze A, Karlas T, Berg T, Wiegand J. Clinical implications of hepatic structure and function evaluation based on vibration-controlled transient elastography and liver maximum function capacity test in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2022; 34:686-692. [PMID: 35102112 DOI: 10.1097/meg.0000000000002347] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIMS Transient elastography [vibration-controlled transient elastography (VCTE)] noninvasively guides risk stratification in patients with nonalcoholic fatty liver disease (NAFLD). Patients with nonalcoholic steatohepatitis (NASH) and fibrosis can be identified using the FAST-score. The liver maximum function test (LiMAx) could be helpful in more precise risk stratification. This pilot study evaluated VCTE, FAST-score, and LiMAx in NAFLD patients. METHODS NAFLD patients prospectively underwent VCTE and LiMAx. The cutoffs for high fibrosis risk were 9.3/9.6 kPa (M/XL-probe) and 331 dB/m for steatosis. A FAST-score greater than 0.67 was used to identify patients with NASH and LiMAx values below 315 μg/kg/h for impaired liver function. RESULTS In total, 57 NAFLD patients (BMI 32 ± 6 kg/m2; 60% diabetes) were included. High risk for fibrosis and steatosis was observed in 26/57 and 28/57 cases, respectively. Overall, 19/57 patients presented impaired liver function. However, 14/26 of patients with a high risk for fibrosis had impaired liver function compared to 5/31 of those without (P = 0.0026). Similarly, 12/18 patients at high risk for NASH had impaired liver function compared to 7/39 without (P < 0.001). The subgroup with diabetes had a liver stiffness a factor of 1.8 higher, FAST-score was 0.13 higher and LiMAx values were 66 μg/kg/h lower compared to nondiabetics. CONCLUSION There is a significant correlation between the functional liver capacity (LiMAx) and the structural liver assessment by VCTE. In cases with high liver stiffness or FAST-score, low LiMAx results may identify NAFLD patients at risk for disease progression and reduce the risk of false-positive categorization.
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Affiliation(s)
- Valentin Blank
- Department of Medicine II, Division of Gastroenterology, Leipzig University Medical Center
- Integrated Research and Treatment Center (IFB) AdiposityDiseases, Faculty of Medicine, University of Leipzig
| | - David Petroff
- Clinical Trial Centre Leipzig, University of Leipzig
| | - Albrecht Boehlig
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Aileen Heinze
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Thomas Karlas
- Department of Medicine II, Division of Gastroenterology, Leipzig University Medical Center
| | - Thomas Berg
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
| | - Johannes Wiegand
- Department of Medicine II, Division of Hepatology, Leipzig University Medical Center, Leipzig, Germany
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17
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Jamialahmadi T, Nematy M, Jangjoo A, Goshayeshi L, Abdalla MA, Akhlaghi S, Sathyapalan T, Sahebkar A. The predictive role of parathyroid hormone for non-alcoholic fatty liver disease based on invasive and non-invasive findings in candidates of bariatric surgery. Eat Weight Disord 2022; 27:693-700. [PMID: 33999371 DOI: 10.1007/s40519-021-01151-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 02/09/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis are the most detrimental hepatic abnormalities associated with increased body weight with devastating clinical outcomes. Therefore, there is a substantial necessity for efficient management strategies, including significant weight reduction. Bariatric surgery has been used as a therapeutic approach in a selected obese patient with NAFLD/NASH and other cardiometabolic comorbidities. PURPOSE The study is focused on the predictive role of PTH with the indices of hepatic steatosis/NAFLD and NASH based on liver biopsy, elastography, and sonography in morbidly obese patients. METHODS Ninety patients with BMI between 35 and 40 kg/m2 with more than two comorbidities who referred to Imam Reza outpatient clinic from December 2016 to September 2017 were recruited and underwent initial assessments, including demographic profiles, psychological assessment, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least two weeks before liver biopsy. The histological analysis of the liver was performed using biopsy samples which obtained from left hepatic lobe during bariatric surgery under direct surgeon observation using a 16-gauge Tru-cut needle. The study was approved by the ethical committee (IR.MUMS.fm.REC.1396.312). RESULTS The level of PTH was significantly high in patients with positive histology for hepatic fibrosis, steatosis, and NASH/NAFLD compared to patients with negative histology (p = 0.005, p = 0.009, and p = 0.013, respectively). Also, patients with liver fibrosis confirmed by elastography had significantly higher serum PTH concentration than patients without fibrosis (p = 0.011). PTH was also positively correlated with hepatic fibrosis, NASH, and steatosis (p = 0.007, p = 0.012, p = 0.023, respectively). CONCLUSION High levels of PTH was significantly associated with histological indices of (hepatic fibrosis, steatosis, NAFLD and NASH) and elasticity indices. Therefore, it is imperative to assess for high levels of PTH in the morbidly obese population pre-and post-bariatric surgery. However, for a more robust and comprehensive assessment, a randomized controlled trial is needed. The study was conducted in accordance with the practice guidance in the diagnosis and management of NAFLD from the American association for the study of liver disease (AASLD) 2018. LEVEL III Evidence obtained from well-designed cohort or case-control analytic studies.
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Affiliation(s)
- Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Nematy
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Jangjoo
- Surgical Oncology Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ladan Goshayeshi
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Gastroenterology and Hepatology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammed Altigani Abdalla
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
| | - Saeed Akhlaghi
- Department of Biostatistics and Epidemiology, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran
- Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thozhukat Sathyapalan
- Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- School of Pharmacy, Mashhad University of Medical Sciences, 9177948564, Mashhad, Iran.
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Segura-Azuara NDLÁ, Varela-Chinchilla CD, Trinidad-Calderón PA. MAFLD/NAFLD Biopsy-Free Scoring Systems for Hepatic Steatosis, NASH, and Fibrosis Diagnosis. Front Med (Lausanne) 2022; 8:774079. [PMID: 35096868 PMCID: PMC8792949 DOI: 10.3389/fmed.2021.774079] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/10/2021] [Indexed: 12/12/2022] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is the most prevalent liver disorder worldwide. Historically, its diagnosis required biopsy, even though the procedure has a variable degree of error. Therefore, new non-invasive strategies are needed. Consequently, this article presents a thorough review of biopsy-free scoring systems proposed for the diagnosis of MAFLD. Similarly, it compares the severity of the disease, ranging from hepatic steatosis (HS) and nonalcoholic steatohepatitis (NASH) to fibrosis, by contrasting the corresponding serum markers, clinical associations, and performance metrics of these biopsy-free scoring systems. In this regard, defining MAFLD in conjunction with non-invasive tests can accurately identify patients with fatty liver at risk of fibrosis and its complications. Nonetheless, several biopsy-free scoring systems have been assessed only in certain cohorts; thus, further validation studies in different populations are required, with adjustment for variables, such as body mass index (BMI), clinical settings, concomitant diseases, and ethnic backgrounds. Hence, comprehensive studies on the effects of age, morbid obesity, and prevalence of MAFLD and advanced fibrosis in the target population are required. Nevertheless, the current clinical practice is urged to incorporate biopsy-free scoring systems that demonstrate adequate performance metrics for the accurate detection of patients with MAFLD and underlying conditions or those with contraindications of biopsy.
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Głuszyńska P, Lemancewicz D, Dzięcioł JB, Razak Hady H. Non-Alcoholic Fatty Liver Disease (NAFLD) and Bariatric/Metabolic Surgery as Its Treatment Option: A Review. J Clin Med 2021; 10:jcm10245721. [PMID: 34945016 PMCID: PMC8706342 DOI: 10.3390/jcm10245721] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/01/2021] [Accepted: 12/03/2021] [Indexed: 12/19/2022] Open
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has considerably increased over the last years. NAFLD is currently the most common cause of chronic liver disease in the developing world. The diagnosis of NAFLD/NASH is often incidental, as the early-stage of disease is frequently free of symptoms. Most patients recognized with NAFLD have severe obesity and other obesity-related disease such as type 2 diabetes mellitus (T2DM), insulin-resistance, dyslipidemia and hypertension. The only proven method for NAFLD improvement and resolution is weight loss. Bariatric surgery leads to significant and long-term weight loss as well as improvement of coexisting diseases. There is a lot of evidence suggesting that metabolic/bariatric surgery is an effective method of NAFLD treatment that leads to reduction in steatosis, hepatic inflammation and fibrosis. However, there is still a need to perform long-term studies in order to determine the role of bariatric surgery as a treatment option for NAFLD and NASH. This review discusses current evidence about epidemiology, pathogenesis and treatment options for NAFLD including bariatric/metabolic surgery and its effect on improvement and resolution of NAFLD.
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Affiliation(s)
- Paulina Głuszyńska
- Department of General and Endocrine Surgery, Medical University of Bialystok, 15-089 Białystok, Poland;
- Correspondence: ; Tel.: +48-85-831-8279
| | - Dorota Lemancewicz
- Department of Human Anatomy, Medical University of Bialystok, 15-089 Białystok, Poland; (D.L.); (J.B.D.)
| | - Janusz Bogdan Dzięcioł
- Department of Human Anatomy, Medical University of Bialystok, 15-089 Białystok, Poland; (D.L.); (J.B.D.)
| | - Hady Razak Hady
- Department of General and Endocrine Surgery, Medical University of Bialystok, 15-089 Białystok, Poland;
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Bhattacharya S, Kalra S, Kapoor N, Singla R, Dutta D, Aggarwal S, Khandelwal D, Surana V, Dhingra A, Kantroo V, Chittawar S, Deka N, Bindal V, Dutta P. Expert opinion on the preoperative medical optimization of adults with diabetes undergoing metabolic surgery. World J Diabetes 2021; 12:1587-1621. [PMID: 34754367 PMCID: PMC8554368 DOI: 10.4239/wjd.v12.i10.1587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/18/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) and obesity are interrelated in a complex manner, and their coexistence predisposes patients to a plethora of medical problems. Metabolic surgery has evolved as a promising therapeutic option for both conditions. It is recommended that patients, particularly those of Asian origin, maintain a lower body mass index threshold in the presence of uncontrolled DM. However, several comorbidities often accompany these chronic diseases and need to be addressed for successful surgical outcome. Laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are the most commonly used bariatric procedures worldwide. The bariatric benefits of RYGB and LSG are similar, but emerging evidence indicates that RYGB is more effective than LSG in improving glycemic control and induces higher rates of long-term DM remission. Several scoring systems have been formulated that are utilized to predict the chances of remission. A glycemic target of glycated hemoglobin < 7% is a reasonable goal before surgery. Cardiovascular, pulmonary, gastrointestinal, hepatic, renal, endocrine, nutritional, and psychological optimization of surgical candidates improves perioperative and long-term outcomes. Various guidelines for preoperative care of individuals with obesity have been formulated, but very few specifically focus on the concerns arising from the presence of concomitant DM. It is hoped that this statement will lead to the standardization of presurgical management of individuals with DM undergoing metabolic surgery.
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Affiliation(s)
| | - Sanjay Kalra
- Endocrinology, Bharti Hospital, Karnal 132001, Haryana, India
| | - Nitin Kapoor
- Endocrinology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - Rajiv Singla
- Endocrinology, Kalpavriksh Super Speciality Center, New Delhi 110075, India
| | - Deep Dutta
- Endocrinology, CEDAR Superspecialty Clinic, New Delhi 110075, India
| | - Sameer Aggarwal
- Endocrinology, Apex Plus Superspeciality Hospital, Rohtak 124001, Haryana, India
| | | | - Vineet Surana
- Endocrinology, Manipal Hospitals, New Delhi 110075, India
| | - Atul Dhingra
- Endocrinology, Gangaram Bansal Super Speciality Hospital, Sri Ganganagar 335001, Rajasthan, India
| | - Viny Kantroo
- Respiratory Medicine & Critical Care, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110076, India
| | - Sachin Chittawar
- Endocrinology, Gandhi Medical College, Bhopal 462001, Madhya Pardesh, India
| | - Nilakshi Deka
- Endocrinology, Apollo Hospitals, Guwahati 781005, Assam, India
| | - Vivek Bindal
- Minimal Access, Metabolic and Bariatric surgery, Max Superspeciality Hospital, Patparganj, New Delhi 110092, India
| | - Puja Dutta
- Nutrition, Max Superspeciality Hospital, Patparganj, New Delhi 110092, India
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21
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Hydes T, Brown E, Hamid A, Bateman AC, Cuthbertson DJ. Current and Emerging Biomarkers and Imaging Modalities for Nonalcoholic Fatty Liver Disease: Clinical and Research Applications. Clin Ther 2021; 43:1505-1522. [PMID: 34400007 DOI: 10.1016/j.clinthera.2021.07.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/15/2021] [Accepted: 07/19/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder that frequently coexists with obesity, metabolic syndrome, and type 2 diabetes. The NAFLD spectrum, ranging from hepatic steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis, can be associated with long-term hepatic (hepatic decompensation and hepatocellular carcinoma) and extrahepatic complications. Diagnosis of NAFLD requires detection of liver steatosis with exclusion of other causes of chronic liver disease. Screening for NAFLD and identification of individuals at risk of end-stage liver disease represent substantial challenges that have yet to be met. NAFLD affects up to 25% of adults, yet only a small proportion will progress beyond steatosis to develop advanced disease (steatohepatitis and fibrosis) associated with increased morbidity and mortality. Identification of this cohort has required the gold standard liver biopsy, which is both invasive and expensive. The use of serum biomarkers and noninvasive imaging techniques is an area of significant clinical relevance. This narrative review outlines current and emerging technologies for the diagnosis of NAFLD, nonalcoholic steatohepatitis, and hepatic fibrosis. METHODS We reviewed the literature using PubMed and reviewed national and international guidelines and conference proceedings to provide a comprehensive overview of the evidence. FINDINGS Significant advances have been made during the past 2 decades that have enhanced noninvasive assessment of NAFLD without the need for liver biopsy. For the detection of steatosis, abdominal ultrasonography remains the first-line investigation, although a controlled attenuation parameter using transient elastography is more sensitive. For detecting fibrosis, noninvasive serum markers of fibrosis and algorithms based on routine biochemistry are available, in addition to transient elastography. These techniques are well validated and have been incorporated into national and international screening guidelines. These approaches have facilitated more judicious use of liver biopsy but are yet to entirely replace it. Although serum biomarkers present a pragmatic and widely available screening approach for NAFLD in large population-based studies, magnetic resonance imaging techniques offer the benefit of achieving high degrees of accuracy in disease grading, tumor staging, and assessing therapeutic response. IMPLICATIONS This diagnostic clinical and research field is rapidly evolving; increasingly combined applications of biomarkers and transient elastography or imaging of selective (intermediate or high risk) cases are being used for clinical and research purposes. Liver biopsy remains the gold standard investigation, particularly in the context of clinical trials, but noninvasive options are emerging, using multimodality assessment, that are quicker, more tolerable, more widely available and have greater patient acceptability.
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Affiliation(s)
- T Hydes
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom; Liverpool University Hospitals National Health Service Foundation Trust, Liverpool, United Kingdom.
| | - E Brown
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom; Liverpool University Hospitals National Health Service Foundation Trust, Liverpool, United Kingdom
| | - A Hamid
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom; Liverpool University Hospitals National Health Service Foundation Trust, Liverpool, United Kingdom
| | - A C Bateman
- Department of Cellular Pathology, Southampton General Hospital, Southampton, United Kingdom
| | - D J Cuthbertson
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom; Liverpool University Hospitals National Health Service Foundation Trust, Liverpool, United Kingdom
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Di Ciaula A, Calamita G, Shanmugam H, Khalil M, Bonfrate L, Wang DQH, Baffy G, Portincasa P. Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests. Int J Mol Sci 2021; 22:7702. [PMID: 34299321 PMCID: PMC8305940 DOI: 10.3390/ijms22147702] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/08/2021] [Accepted: 07/14/2021] [Indexed: 02/07/2023] Open
Abstract
The liver plays a key role in systemic metabolic processes, which include detoxification, synthesis, storage, and export of carbohydrates, lipids, and proteins. The raising trends of obesity and metabolic disorders worldwide is often associated with the nonalcoholic fatty liver disease (NAFLD), which has become the most frequent type of chronic liver disorder with risk of progression to cirrhosis and hepatocellular carcinoma. Liver mitochondria play a key role in degrading the pathways of carbohydrates, proteins, lipids, and xenobiotics, and to provide energy for the body cells. The morphological and functional integrity of mitochondria guarantee the proper functioning of β-oxidation of free fatty acids and of the tricarboxylic acid cycle. Evaluation of the liver in clinical medicine needs to be accurate in NAFLD patients and includes history, physical exam, imaging, and laboratory assays. Evaluation of mitochondrial function in chronic liver disease and NAFLD is now possible by novel diagnostic tools. "Dynamic" liver function tests include the breath test (BT) based on the use of substrates marked with the non-radioactive, naturally occurring stable isotope 13C. Hepatocellular metabolization of the substrate will generate 13CO2, which is excreted in breath and measured by mass spectrometry or infrared spectroscopy. Breath levels of 13CO2 are biomarkers of specific metabolic processes occurring in the hepatocyte cytosol, microsomes, and mitochondria. 13C-BTs explore distinct chronic liver diseases including simple liver steatosis, non-alcoholic steatohepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug, and alcohol effects. In NAFLD, 13C-BT use substrates such as α-ketoisocaproic acid, methionine, and octanoic acid to assess mitochondrial oxidation capacity which can be impaired at an early stage of disease. 13C-BTs represent an indirect, cost-effective, and easy method to evaluate dynamic liver function. Further applications are expected in clinical medicine. In this review, we discuss the involvement of liver mitochondria in the progression of NAFLD, together with the role of 13C-BT in assessing mitochondrial function and its potential use in the prevention and management of NAFLD.
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Affiliation(s)
- Agostino Di Ciaula
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (A.D.C.); (H.S.); (M.K.); (L.B.)
| | - Giuseppe Calamita
- Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari “Aldo Moro”, 70100 Bari, Italy;
| | - Harshitha Shanmugam
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (A.D.C.); (H.S.); (M.K.); (L.B.)
| | - Mohamad Khalil
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (A.D.C.); (H.S.); (M.K.); (L.B.)
| | - Leonilde Bonfrate
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (A.D.C.); (H.S.); (M.K.); (L.B.)
| | - David Q.-H. Wang
- Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA;
| | - Gyorgy Baffy
- Department of Medicine, VA Boston Healthcare System and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02130, USA;
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (A.D.C.); (H.S.); (M.K.); (L.B.)
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23
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Haufe S, Hupa-Breier KL, Bayerle P, Boeck HT, Rolff S, Sundermeier T, Kerling A, Eigendorf J, Kück M, Hanke AA, Ensslen R, Nachbar L, Lauenstein D, Böthig D, Hilfiker-Kleiner D, Stiesch M, Terkamp C, Wedemeyer H, Haverich A, Tegtbur U. Telemonitoring-Supported Exercise Training in Employees With Metabolic Syndrome Improves Liver Inflammation and Fibrosis. Clin Transl Gastroenterol 2021; 12:e00371. [PMID: 34140456 PMCID: PMC8216678 DOI: 10.14309/ctg.0000000000000371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 04/28/2021] [Indexed: 01/03/2023] Open
Abstract
INTRODUCTION Metabolic syndrome (MetS) is a major health problem worldwide and the main risk factor for metabolic-associated fatty liver disease (MAFLD). Established treatment options are lifestyle interventions facilitating dietary change and increased physical activity. Here, we tested the effect of a telemonitoring-supported intervention on liver parameter of inflammation and fibrosis in individuals with MetS. METHODS This was a prospective, randomized, parallel-group, and assessor-blind study performed in workers of the main Volkswagen factory (Wolfsburg, Germany). Volunteers with diagnosed MetS were randomly assigned (1:1) to a 6-month lifestyle intervention focusing on supervised, activity-tracker-guided exercise or to a waiting-list control group. This secondary analysis assessed the effect of the intervention on liver enzymes and MAFLD-related parameters. RESULTS We screened 543 individuals between October 10, 2017, and February 27, 2018, of whom 314 were randomly assigned to the intervention group (n = 160) or control group (n = 154). Liver transaminases, alkaline phosphatase, and gamma-glutamyl transferase significantly decreased after 6 months in the intervention group compared with the CG. Furthermore, an aspartate aminotransferase-to-platelet ratio index score as a marker for liver fibrosis significantly decreased in the intervention group. These improvements were associated with changes in obesity and exercise capacity. DISCUSSION A 6-month lifestyle intervention based on exercise training with individualized telemonitoring-based supervision led to improvements of liver inflammation and fibrosis in employees with MetS. Therefore, this intervention shows therapeutic potential for individuals at high risk of MAFLD (ClinicalTrials.gov Identifier: NCT03293264).
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Affiliation(s)
- Sven Haufe
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
- Institute of Sports Science, Leibniz University Hannover, Hannover, Germany;
| | - Katharina L. Hupa-Breier
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany;
| | - Pauline Bayerle
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
| | - Hedwig T. Boeck
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
| | - Simone Rolff
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
| | | | - Arno Kerling
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
| | - Julian Eigendorf
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
| | - Momme Kück
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
| | - Alexander A. Hanke
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
| | | | | | | | - Dietmar Böthig
- Department of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Germany;
| | | | - Meike Stiesch
- Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School, Hannover, Germany.
| | - Christoph Terkamp
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany;
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany;
| | - Axel Haverich
- Department of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Germany;
| | - Uwe Tegtbur
- Institute of Sports Medicine, Hannover Medical School, Hannover, Germany;
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Comparison of Liver Recovery After Sleeve Gastrectomy and Roux-en-Y-Gastric Bypass. Obes Surg 2021; 31:3218-3226. [PMID: 33813683 PMCID: PMC8175244 DOI: 10.1007/s11695-021-05390-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 03/21/2021] [Accepted: 03/25/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a common condition in patients with obesity. Bariatric surgery has often been proposed as a viable treatment option, but the ideal surgical procedure remains unclear. Inconsistently, reports on postoperative deterioration of liver function put further doubt on which technique to apply. Aim of this study was to assess the impact of Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) on the postoperative recovery of liver function. METHODS A total of 175 patients with obesity that underwent bariatric surgery in our institution were included in this prospective cohort study. BMI, laboratory values, and liver function capacity (using LiMAx) were assessed preoperatively and at 6 and 12 months postoperatively. Generalized linear model (GLM) was performed to determine variables influencing liver function capacity after the operation. RESULTS Prior to operations, 64% of patients presented with a diminished liver function capacity, as measured by LiMAx test. Liver function capacity significantly recovered after 12 months in the SG group (300 μg/kg/h preop vs. 367 μg/kg/h postop) but not in the RYGB group (306 μg/kg/h preop vs. 349 μg/kg/h). Preoperative factors impeding liver function recovery included type 2 diabetes mellitus (T2DM), weight, male sex, AST/thrombocyte ratio (APRI), and gamma-glutamyltransferase (GGT). CONCLUSION Bariatric surgery, especially sleeve gastrectomy, leads to an improvement of liver function. However, in some patients with T2DM, higher preoperative weight and male sex postoperative deterioration of liver function capacity may occur.
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Development and validation of a noninvasive clinical scoring system to predict significant fibrosis in patients with nonalcoholic fatty liver disease. Clin Chim Acta 2020; 514:48-53. [PMID: 33333040 DOI: 10.1016/j.cca.2020.12.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 11/27/2020] [Accepted: 12/08/2020] [Indexed: 01/22/2023]
Abstract
BACKGROUND The aims of this study were to identify risk factors for significant fibrosis (SF) by assessing physical and laboratory parameters and develop and validate a clinical score and nomogram for the prediction of SF in patients with nonalcoholic fatty liver disease (NAFLD). METHODS This retrospective study included 225 patients with histologically confirmed NAFLD who were divided into two cohorts using 10-fold cross validation for model training and validation. The clinical score and nomogram were used to predict the NAFLD outcome. RESULTS The model for predicting SF (stage ≥ 2) including the free T4/free T3 ratio, low-density lipoprotein cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), percentage of appendicular skeletal muscle mass and aspartate aminotransferase (AST) level in the training and validation cohorts yielded an area under the receiver operator characteristic curve (AUROC) of 0.79 and 0.78, respectively. The AUROC of the combined clinical score for the prediction of SF was 0.82 (95% CI, 0.75-0.89) at a cutoff value of 3 points, with a sensitivity (SE) of 77.19%, specificity (SP) of 82.88%, positive predictive value (PPV) of 63.77%, and negative predictive value (NPV) of 90.30%. The nomogram had good performance in quantitatively predicting the risk probability of SF. CONCLUSION Our study showed that a noninvasive clinical scoring system using easily available physical and laboratory variables can identify patients with NAFLD with or without SF with a high degree of accuracy. Application of this system may decrease the need for staging liver biopsy specimens and allow early identification and intervention in these high-risk patients.
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